What drugs to start with

The guidelines stress the importance of selecting the best regimen for the individual patient. Before ARV therapy begins, a baseline assessment should include resistance testing; screening for hepatitis B and C, presence or history of heart disease, diabetes and renal problems; and psychiatric disease. Lifestyle issues such as alcohol and drug use should be discussed and for women of childbearing age, pregnancy plans and contraception.

The ideal regimen is one that the patient fully understands and can incorporate into their daily life, while taking into account its potency, durability, tolerability, convenience, toxicity profile, and cost. The goal of treatment is to achieve a viral load of less than 50 copies/ml within four to six months of starting treatment.

Two nucleoside reverse transcriptase inhibitors (NRTIs) + an NNRTI

• Efavirenz-based ART is the first-line choice for therapy-naive patients. Either Truvada (tenofovir + emtricitabine/FTC) or Kivexa (lamivudine/3TC + abacavir) are appropriate first-choice nucleoside backbones.
• Kivexa should only be used in patients who are HLA-B*5701 negative and used with caution in patients with baseline viral loads over 100,000 copies/ml or a significant cardiovascular risk.
• If psychiatric problems exist, efavirenz should be avoided. Nevirapine can be used in women with a CD4 count <250 cells/mm³ and in men whose cell count is <400 cells/mm³.
• For prevention of transmission from mother-to-child (PTMTC) when a woman is not on ARV therapy for her own health, Combivir (zidovudine/AZT + 3TC) is the treatment of choice. For a woman who is on ARV therapy and becomes pregnant, nevirapine can be used as an alternative for efavirenz. This requires a 14-day induction period unless switching directly from efavirenz.

Atripla combines tenofovir + FTC + efavirenz, but is only licensed by the European Medicines Agency (EMEA) for use in virologically suppressed patients.

Two NRTIs + a boosted protease inhibitor (PI)

Boosted PIs should be reserved for situations in which:

• Primary reverse transcriptase resistance is suspected.

• A woman wants to become pregnant.

• Psychiatric problems exist.

When a PI is used for an initial HAART regimen, it should be a boosted agent. This results in increased drug exposure (thus extending the drug’s half-life, reducing dosing frequency, and pill burden, and limiting the development of resistance).

Regimen possibilities include lopinavir, fosamprenavir, or saquinavir, each boosted with ritonavir. The PI would be combined with two NRTIs. Possibilities include one of the following drugs (tenofovir, abacavir, didanosine), or zidovudine, plus either 3TC or FTC. 

Fixed-dose combinations of the two NRTIs are Truvada (tenofovir + FTC), Kivexa (3TC + abacavir), and Combivir (3TC/AZT).